不同剂量左旋甲状腺素钠预处理对幼龄大鼠心肌缺血再灌注损伤的影响
불동제량좌선갑상선소납예처리대유령대서심기결혈재관주손상적영향
Effects of preconditioning with different doses of levothyroxine sodium on myocardial ischemia-reperfusion injury in immature rats
  • 万方数据
    中华麻醉学杂志 중화마취학잡지
    CHINESE JOURNAL OF ANESTHESIOLOGY
    2011年 5期 616-620 ,共5页

    杨泉涌%薛富善%许亚超%张霖%罗艺%廖旭%熊军%李杉%张雁鸣

    양천용%설부선%허아초%장림%라예%료욱%웅군%리삼%장안명

    甲状腺激素类%缺血预处理%心肌再灌注损伤%儿童 甲狀腺激素類%缺血預處理%心肌再灌註損傷%兒童
    갑상선격소류%결혈예처리%심기재관주손상%인동
    Thyroid hormones%Ischemic preconditioning%Myocardial reperfusion injury%Child
    目的 评价不同剂量左旋甲状腺素钠预处理对幼龄大鼠心肌缺血再灌注损伤的影响.方法 健康雌性 Wistar大鼠48只,日龄35 d,体重120～140 g,采用随机数字表法,将其随机分为6组(n=8):对照组(C组)、缺血再灌注组(I/R组)和不同剂量左旋甲状腺素钠预处理组(LS1-4组).C组和I/R组大鼠采用普通饲料喂养7 d;LS1-4组大鼠除了采用普通饲料喂养之外,每天胃内灌注左旋甲状腺素钠10、20、40和80 μg/100 g.第8天时,抽取外周静脉血样,测定血清甲状腺激素水平.采用Langendorff装置建立大鼠离体心脏缺血再灌注模型.C组K-H液持续灌注80 min;其余各组K-H液平衡灌注30 min,然后全心缺血20 min,恢复灌注30 min.于平衡灌注20 min和再灌注30 min时,记录HR、SP、左心室内压最大上升速率(+dp/dtmax)和左心室内压最大下降速率(-dp/dtmax),计算再灌注30min时HR、SP、+dp/dtmax和-dp/dtmax的恢复率.于平衡灌注10 min和再灌注15 min时,收集冠状动脉流出液2 ml,测定CK-MB的活性.再灌注30 min时,取心室肌组织,采用Western blot法检测心肌热休克蛋白70(HSPT0)的表达,采用RT-PCR法测定甲状腺激素受体(TR)亚型(TRα1、TRα2和TRβ1)mRNA以及肌球蛋白重链α和β(MHCα和MHCβ)mRNA的表达.结果 与C组相比,I/R组HR、SP和±dp/dtmax的恢复率降低,冠脉流出液CK-MB活性升高,心肌MHCα mRNA表达下调,LS1-4组SP和±dp/dtmax的恢复率降低,冠脉流出液CK-MB活性升高,心肌HSP70和MHCα mRNA表达上调,LS2-4组血清甲状腺激素水平升高,心肌TRα1 mRNA表达上调(P＜0.05).与I/R组相比,LS1-4组HR和±dp/dtmax的恢复率升高,心肌HSP70表达上调,MHCa mRNA表达上调,MHCβ mRNA表达下调,LS1-3组冠脉流出液CK-MB活性降低,LS2-4组血清甲状腺激素水平升高,心肌TRα1 mRNA表达上调(P＜0.05).LS1组、LS2组、LS3组和LS4组的甲状腺激素血清水平随左旋甲状腺素钠剂量的增加逐渐升高(P＜0.05).与LS1组和LS2组相比,LS3组和LS4组冠脉流出液CK-MB活性升高,心肌HSP70表达下调(P＜0.05).结论 10 μg/100 g左旋甲状腺素钠胃内灌注预处理可减轻大鼠心肌缺血再灌注损伤,且不会导致甲状腺激素水平升高,其机制可能与心肌HSP70和MHCα mRNA表达上调有关.
    목적 평개불동제량좌선갑상선소납예처리대유령대서심기결혈재관주손상적영향.방법 건강자성 Wistar대서48지,일령35 d,체중120～140 g,채용수궤수자표법,장기수궤분위6조(n=8):대조조(C조)、결혈재관주조(I/R조)화불동제량좌선갑상선소납예처리조(LS1-4조).C조화I/R조대서채용보통사료위양7 d;LS1-4조대서제료채용보통사료위양지외,매천위내관주좌선갑상선소납10、20、40화80 μg/100 g.제8천시,추취외주정맥혈양,측정혈청갑상선격소수평.채용Langendorff장치건립대서리체심장결혈재관주모형.C조K-H액지속관주80 min;기여각조K-H액평형관주30 min,연후전심결혈20 min,회복관주30 min.우평형관주20 min화재관주30 min시,기록HR、SP、좌심실내압최대상승속솔(+dp/dtmax)화좌심실내압최대하강속솔(-dp/dtmax),계산재관주30min시HR、SP、+dp/dtmax화-dp/dtmax적회복솔.우평형관주10 min화재관주15 min시,수집관상동맥류출액2 ml,측정CK-MB적활성.재관주30 min시,취심실기조직,채용Western blot법검측심기열휴극단백70(HSPT0)적표체,채용RT-PCR법측정갑상선격소수체(TR)아형(TRα1、TRα2화TRβ1)mRNA이급기구단백중련α화β(MHCα화MHCβ)mRNA적표체.결과 여C조상비,I/R조HR、SP화±dp/dtmax적회복솔강저,관맥류출액CK-MB활성승고,심기MHCα mRNA표체하조,LS1-4조SP화±dp/dtmax적회복솔강저,관맥류출액CK-MB활성승고,심기HSP70화MHCα mRNA표체상조,LS2-4조혈청갑상선격소수평승고,심기TRα1 mRNA표체상조(P＜0.05).여I/R조상비,LS1-4조HR화±dp/dtmax적회복솔승고,심기HSP70표체상조,MHCa mRNA표체상조,MHCβ mRNA표체하조,LS1-3조관맥류출액CK-MB활성강저,LS2-4조혈청갑상선격소수평승고,심기TRα1 mRNA표체상조(P＜0.05).LS1조、LS2조、LS3조화LS4조적갑상선격소혈청수평수좌선갑상선소납제량적증가축점승고(P＜0.05).여LS1조화LS2조상비,LS3조화LS4조관맥류출액CK-MB활성승고,심기HSP70표체하조(P＜0.05).결론 10 μg/100 g좌선갑상선소납위내관주예처리가감경대서심기결혈재관주손상,차불회도치갑상선격소수평승고,기궤제가능여심기HSP70화MHCα mRNA표체상조유관.
    Objective To investigate the effects of preconditioning with different doses of levothyroxine sodium on myocardial ischemia-reperfusion (I/R) injury in immature rats. Methods Forty-eight female immature Wistar rats, aged 35 days, weighing 120-140 g, were randomly allocated into 6 groups ( n = 8 each): control group (group C), I/R group, and preconditioning with levothyroxine sodium 10, 20, 40 and 80 μg/100 g groups (groups LS1-4 ) . The rats received levothyroxine sodium 10, 20, 40 and 80 μg/100 g through a gastric tube every day for 7 days in groups LS1-4 , respectively. Venous blood samples were taken on 8th day for determination of serum thyroid hormone levels. The hearts were removed from the animals and perfused in a Langendorff apparatus with K-H solution saturated with 95% O2-5% CO2 at 37 ℃. The hearts were continuously perfused for 80 min in group C. After 30 min of equilibration, the isolated hearts were subjected to 20 min of ischemia followed by 30 min of reperfusion in I/R and LS1-4 groups. HR, SP and ± dp/dtmax were recorded at 20 min of perfusion and 30 min of reperfusion. The recovery rates of HR, SP and ± dp/dtmax were calculated at 30 min of reperfusion. The coronary effluent was collected at 10 min of perfusion and 15 min of reperfusion for determination of creatine kinase (CKMB) activity. The samples of ventricular myocardial tissues were taken at 30 min of reperfusion to detect the expression of heat shock protein 70 (HSP70), thyroid hormone receptor (TR) mRNA (TRa, , TRoj and TRft ) and myosin heavy chain (MHC) mRNA. Results Compared with group C, the recovery rates of HR, SP and. ± dp/dtmax were significantly decreased, the CK-MB activity was significantly increased, and MHCα mRNA expression was down-regulated in group I/R, the recovery rates of SP and ± dp/dtmax were significantly decreased, the CK-MB activity was significantly increased, and the expression of HSP70 and MHCα mRNA was up-regulated in groups LS1-4, and the serum thyroid hormone level was significantly increased and the expression of TRa, mRNA was up-regulated in groups LS2-4 ( P ＜ 0.05) . Compared with group I/R, the recovery rates of HR and ± dp/dtmax were significantly increased, the pression of HSP70 and MHCa mRNA was up-regulated, and the MHCJ3 mRNA expression was down-regulated in groups LS1-4 the CK-MB activity was significantly decreased in groups LS1-3, and the serum thyroid hormone level was significantly increased and the expression of TRα1, mRNA was up-regulated in groups LS2-4 ( P ＜ 0.05) . The serum thyroid hormone level increased gradually with the increase in the dose of levothyroxine sodium in groups LS1-4 ( P ＜ 0.05) . The CK-MB activity was significantly higher, while the HSP70 expression lower in groups LS3-4 than in groups LS1-2 (P ＜ 0.05). Conclusion Preconditioning with levothyroxine sodium 10 μg/100 g can alleviate the myocardial I/R injury in immature rats and does not lead to the increase in the level of thyroid hormone, and the up-regulation of HSP70 and MHCa mRNA expression may be involved in the mechanism.
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